Molecular diversity and phylogeny of Hantaan virus in Guizhou, China: evidence for Guizhou as a radiation center of the present Hantaan virus

Abstract

To gain further insight into the molecular epidemiology of Hantaan virus (HTNV) in Guizhou, China, rodents were captured in this region in 2004 and 2005. In addition, serum samples were collected from four patients. Ten hantaviruses were isolated successfully in cell culture from four humans, two Apodemus agrarius, three Rattus norvegicus and one Rattus nitidus. The nucleotide sequences for their small (S), medium (M) and partial large (L) segments were determined. Phylogenetic analysis of the S and M segment sequences revealed that all of these isolates belong to the species HTNV, suggesting a spillover of HTNV from A. agrarius to Rattus rats. All available isolates from Guizhou were divided into four distinct groups either in the S segment tree or in the M segment tree. The clustering pattern of these isolates in the S segment tree was not in agreement with that in the M or L segment tree, showing that genetic reassortment between HTNV had occurred naturally. Analysis of the S segment sequences from available HTNV strains indicated that they formed three clades. The first clade, which comprised only viruses from Guizhou, was the outgroup of clades II and III. The viruses in the second clade were found in Guizhou and mainly in the far-east Asian region, including China. However, the viruses in the third clade were found in most areas of China, including Guizhou, in which haemorrhagic fever with renal syndrome (HFRS) is endemic. Our results reveal that the highest genetic diversity of HTNV is in a limited geographical region of Guizhou, and suggest that Guizhou might be a radiation centre of the present form of HTNV. INTRODUCTIONHaemorrhagic fever with renal syndrome (HFRS) is an important human disease; 60 000 to 100 000 cases requiring hospitalization are reported annually worldwide, with the majority occurring in China (Johnson, 1999;Zhang et al., 2004). The disease is caused by hantaviruses, members of the genus Hantavirus in the family Bunyaviridae (Nichol et al., 2005). The virus genome consists of three separate segments of negative-stranded RNA referred to as small (S), medium (M), and large (L) segments, which encode nucleocapsid protein (NP), two envelope glycoproteins (Gn and Gc) and viral RNA-dependent RNA polymerase (RdRP), respectively (Plyusnin et al., 1996). In contrast to other genera of the Bunyaviridae, hantaviruses are not transmitted by arthropods (Schmaljohn & Hjelle, 1997). They establish a chronic infection that causes no apparent harm to rodents of the Muridae family, which are their natural hosts (Childs et al., 1989; Hutchinson et al., 2000;Kurata et al., 1983;Li et al., 1995;Netski et al., 1999). Currently, at least 22 distinct hantavirus species have been identified worldwide; all of these hantaviruses except Thottapalayam virus (TPMV) are carried by rodents (Nichol et al., 2005). Each rodent-borne hantavirus species appears to be associated primarily with one (or a few closely related) rodent species (Nichol et al., 2005; Plyusnin GenBank accession numbers of the S, M and L segment...

Isolation and Characterization of Hantaviruses in Far East Russia and Etiology of Hemorrhagic Fever with Renal Syndrome in the Region

“…In the present study, the S, M, and L segments of AP209 clustered with AMRVs in lineages S6, M6, and L5, respectively, consistent with the results in the work by Zou and others. 30 AP209 was more related to AMRVs detected in the Primorsky region of Far East Russia, such as AP708, AP1371, AP1168, Solovey/AP61/1999, and Solovey/AP63/1999, than AMRVs from China and Korea. Although the M and L segments of AMRV clustered in distinct lineages from other HTNVs, the S segment of AMRV clustered within HTNV.…”

“…Previously, the work by Zou and others 30 described that the Hantaan superclade, including HTNV and AMRV, was divided into several lineages, and the S, M, and L segments of AMRV occupied lineages S6, M6, and L5, respectively. In the present study, the S, M, and L segments of AP209 clustered with AMRVs in lineages S6, M6, and L5, respectively, consistent with the results in the work by Zou and others.…”

“…This observation was also reported in the work by Zou and others. 30 Previous reports of phylogenetic analysis have indicated that a natural reassortment occurred between HTNV and SEOV in China and among different lineages of PUUVs in nature. 31,32 Additionally, dual infection with Sin Nombre virus and Black Creek Canal virus could produce reassortant viruses under experimental conditions.…”

The Ecology, Genetic Diversity, and Phylogeny of Huaiyangshan Virus in China

“…Every sublineage except sublineage D included strains identified from Ն3 provinces that are approximately 1,300 to 3,200 km from the Huaiyangshan mountainous region. These data suggest that HYSV species do not exhibit a geographic clustering pattern such as is seen with zoonotic viruses such as hantavirus and rabies virus (4,18).…”

An Efficient Method for Isolation of Hantaan Virus through Serial Passages in Suckling Mice

“…Among rodent-borne hantaviruses, Hantaan virus (HTNV) is one of main causative agents of HFRS in Asia, especially in China [8,9]. HFRS poses a serious public health problem in China and HTNV has been found in all Chinese provinces except Xinjiang.…”